Two Promising Drugs for Symptomatic Uterine Leiomyomas

Although symptomatic uterine leiomyomas (fibroids) are common, effective therapies are few. Now, two industry-supported trials provide evidence that ulipristal acetate (a selective progesterone receptor modulator) and elagolix (a gonadotropin-releasing hormone [GnRH] antagonist) may have roles for managing leiomyomas in women who want to avoid surgical intervention.

In the ulipristal study, 432 premenopausal women (mean age, 41; 70% black) were randomized to once-daily 5-mg ulipristal, 10-mg ulipristal, or placebo in two 12-week treatment courses separated by an interval of two menses. In course 1, amenorrhea was achieved by 42% and 55% of women in the 5-mg and 10-mg groups, respectively, compared with 0% in the placebo group (P<0.001 for each dose). Most women became amenorrheic within 10 days of receiving ulipristal, which was well tolerated. Significant improvements in quality of life were noted with both doses of ulipristal compared with placebo. Leiomyoma volume decreased significantly during the first course of ulipristal and continued to diminish during the second course.

In the elagolix safety and efficacy trial, 567 premenopausal women (mean age, 43; 72% black) received elagolix (300 mg twice daily [cohort 1] or 600 mg once daily [cohort 2]); within each dosing cohort, women received placebo, elagolix alone, or elagolix with add-back therapy (0.5 mg estradiol/0.1 mg norethindrone acetate or 1.0 mg estradiol/0.5 mg norethindrone acetate). The primary endpoint (<80 mL menstrual blood loss and ≥50% reduction in menstrual blood loss from baseline) was achieved by 92% (cohort 1) and 90% (cohort 2) of women receiving elagolix alone, 85% and 73% of women receiving elagolix plus the lower add-back dose, and 79% and 82% of women receiving elagolix plus the higher add-back dose, compared with 27% and 32% of those who received placebo (all P<0.001 vs. placebo).Women receiving elagolix (except those receiving the higher dose of add-back therapy) had significant decreases from baseline in lumbar spine bone mineral density. All elagolix groups (except cohort 2 with high-dose add-back therapy) had significant decreases in leiomyoma volume.